Pembrolizumab + AR Inhibitors for Prostate Cancer
What You Need to Know Before You Apply
What is the purpose of this trial?
This trial explores whether a new combination of treatments can more effectively combat prostate cancer. Researchers are testing if adding a drug that targets cancer cells with radiation (225Ac-J591, an alpha-PSMA-targeted radionuclide therapy) to a mix of an immunotherapy drug (pembrolizumab) and hormone therapy (androgen receptor inhibitor or ARI) is more effective than the immunotherapy and hormone therapy alone. The trial targets men with prostate cancer that has spread and continues to grow despite treatment. Those who have previously tried treatments like enzalutamide or abiraterone and have experienced progression might be suitable candidates. As a Phase 1, Phase 2 trial, this research aims to understand how the treatment works in people and measure its effectiveness in an initial, smaller group, offering participants a chance to contribute to groundbreaking advancements in prostate cancer therapy.
Will I have to stop taking my current medications?
The trial does not specify if you need to stop taking your current medications. However, you must continue primary androgen deprivation therapy if you haven't had an orchiectomy, and you can stay on bisphosphonates or denosumab if you've been on a stable dose for at least 4 weeks before starting the trial.
Is there any evidence suggesting that this trial's treatments are likely to be safe?
Research has shown that 225Ac-J591 is generally well-tolerated. In one study, many patients experienced a drop in prostate-specific antigen (PSA) levels, a marker used to monitor prostate cancer. Common side effects included fatigue and low blood cell counts.
Androgen receptor inhibitors (ARIs) also treat prostate cancer and can cause side effects such as tiredness, weight gain, and hot flashes. Some studies have noted a higher risk of heart-related issues.
Pembrolizumab has demonstrated general safety. It can cause side effects like fatigue and skin rash but is usually considered safe for many patients.
In summary, each component of this treatment has undergone safety testing in humans. While side effects can occur, they are usually manageable. Always consult a doctor to understand what this means for your health.12345Why are researchers excited about this trial's treatments?
Researchers are excited about these treatments for prostate cancer because they bring innovative approaches to combatting the disease. Unlike most standard treatments like hormone therapy or chemotherapy, the combination of Pembrolizumab with 225Ac-J591 and androgen receptor inhibitors (ARIs) uses a targeted radiolabeled antibody, 225Ac-J591, to specifically attack cancer cells. Moreover, Pembrolizumab, an immune checkpoint inhibitor, boosts the body's immune system to fight the cancer, which is not a feature of traditional treatments. This combination has the potential to enhance the effectiveness of ARIs, like enzalutamide, apalutamide, or darolutamide, by not only blocking cancer-promoting signals but also directly targeting and destroying cancer cells.
What evidence suggests that this trial's treatments could be effective against prostate cancer?
Research has shown that pembrolizumab, when combined with enzalutamide (a drug that blocks male hormones), has limited success in treating advanced prostate cancer that no longer responds to standard hormone therapy. This suggests it might not control the cancer effectively on its own. In this trial, one group of participants will receive pembrolizumab and an androgen receptor pathway inhibitor (ARI) like enzalutamide. Another group will receive pembrolizumab, ARI, and 225Ac-J591, a targeted radiation treatment. Adding 225Ac-J591 aims to improve outcomes by delivering radiation directly to prostate cancer cells. Previous studies on similar treatments have suggested that targeting a specific protein on prostate cancer cells with radiation can help slow the cancer's progression. This combination approach is promising because it might enhance the immune system's ability to fight cancer while also directly attacking cancer cells with radiation.678910
Who Is on the Research Team?
Scott Tagawa, MD, MS
Principal Investigator
Weill Medical College of Cornell University
Are You a Good Fit for This Trial?
Men over 18 with advanced prostate cancer that's resistant to hormone therapy and has progressed after certain treatments. They must have a good performance status, normal organ function, and agree to contraception during the trial plus 4 months after. Exclusions include other cancers within 2 years, active infections like HIV or hepatitis, recent blood clots or radiotherapy, autoimmune diseases requiring treatment in the last 2 years, current participation in another study drug trial.Inclusion Criteria
Exclusion Criteria
Timeline for a Trial Participant
Screening
Participants are screened for eligibility to participate in the trial
Treatment Phase I
Participants receive pembrolizumab, ARPI, and a single dose of 225Ac-J591 to determine the optimal dose
Safety Follow-up
Safety follow-up to monitor dose-limiting toxicity and determine optimal dose for phase II
Treatment Phase II
Randomized treatment with pembrolizumab and ARPI, with or without 225Ac-J591
Follow-up
Participants are monitored for safety and effectiveness after treatment
What Are the Treatments Tested in This Trial?
Interventions
- 225Ac-J591
- Androgen receptor pathway inhibitor
- Pembrolizumab
Find a Clinic Near You
Who Is Running the Clinical Trial?
Weill Medical College of Cornell University
Lead Sponsor
Merck Sharp & Dohme LLC
Industry Sponsor
Chirfi Guindo
Merck Sharp & Dohme LLC
Chief Marketing Officer since 2022
Degree in Engineering from Ecole Centrale de Paris, MBA from New York University Stern School of Business
Robert M. Davis
Merck Sharp & Dohme LLC
Chief Executive Officer since 2021
JD from Northwestern University Pritzker School of Law, MBA from Northwestern University Kellogg Graduate School of Management, Bachelor's in Finance from Miami University
United States Department of Defense
Collaborator